Flow cytometry is a data-rich technology that plays a critical role in basic research and clinical diagnostics for a variety of human diseases. Traditionally, the majority of cytometry experiments have been analyzed visually, either by serial inspection of one or two dimensions (markers) at a time (a process termed gating, with boundaries or gates defining cell populations of interest), or by very basic comparisons of summary statistics. Technological advances in cytometry based on atomic mass spectrometry will soon allow researchers to query up to 50 markers (as opposed to about 10 with current technology), making traditional analysis approaches untenable. This new mass cytometry technology will generate high-throughput high-dimensional datasets, opening up new avenues for single--cell biology. As a consequence, it is essential that analytical tools and statistical methods take part in this revolution to harness the full potential of the technology. We are proposing novel computational methods and software tools for both flow and mass cytometry. The impact of these tools will be to provide researchers with a set of tools that will become essential to extract meaningful information from such data. We will apply our methods to a number of different scenarios such as the identification of immune correlate of protections for HIV and malaria vaccines, the identification of genetic mechanisms of homeostasis, and the clinical prediction of chronic inflammatory conditions. PUBLIC HEALTH RELEVANCE: The aims of this project are to develop statistical and computational methods for the analysis of flow and mass cytometry data and apply these to large datasets issued from clinical trials. The impact of these tools will be to provide researcher with a set of tools that will become essential to extract meaningful information from such data. The domain of applications spans all diseases, and our current application covers multiple diseases including HIV, malaria and inflammatory conditions.